Resveratrol protects against heatstroke and the complicated liver injury by inhibiting HSF1.
Source: PubMed, NCBI / U.S. National Library of Medicine
As global warming intensifies, heatstroke and complicated liver injury are increasingly becoming the most serious clinical manifestations of heat-related illnesses. However, effective intervention strategies are lacking. This study aims to investigate the protective effect of resveratrol against heatstroke and complicated liver injury and elucidates its molecular mechanism. In this study, a mouse heatstroke model and an AML12 hepatocyte heat exposure model were established. Resveratrol, HSF1 agonist (HSF1A), HSF1 inhibitor (KRIBB11), and HSF1 knockdown were administeredand/orto investigate the role of HSF1 and validate the core mechanism by which resveratrol protects against liver injury induced by heat exposure. The results showed that resveratrol pretreatment significantly attenuated temperature dysregulation, liver morphology and function induced by heat exposure. Heat exposure upregulated HSF1 expression in both the mouse liver and hepatocytes. HSF1 activation (agonist HSF1A) caused liver injury, lipid deposition and necroptosis typically induced by heat exposure, while HSF1 inhibition and HSF1 knockout reduced these effects. Resveratrol showed the potential to bind to HSF1 and inhibit HSF1 expression in the liver. Moreover, it protected against heat-induced lipid metabolic disorders and necroptosis bothand, in which necroptosis inhibition did not alter lipid metabolism in hepatocytes. Finally, HSF1 inhibitor (KRIBB11) administration protected against heat stroke and live
Abstract
As global warming intensifies, heatstroke and complicated liver injury are increasingly becoming the most serious clinical manifestations of heat-related illnesses. However, effective intervention strategies are lacking. This study aims to investigate the protective effect of resveratrol against heatstroke and complicated liver injury and elucidates its molecular mechanism. In this study, a mouse heatstroke model and an AML12 hepatocyte heat exposure model were established. Resveratrol, HSF1 agonist (HSF1A), HSF1 inhibitor (KRIBB11), and HSF1 knockdown were administeredand/orto investigate the role of HSF1 and validate the core mechanism by which resveratrol protects against liver injury induced by heat exposure. The results showed that resveratrol pretreatment significantly attenuated temperature dysregulation, liver morphology and function induced by heat exposure. Heat exposure upregulated HSF1 expression in both the mouse liver and hepatocytes. HSF1 activation (agonist HSF1A) caused liver injury, lipid deposition and necroptosis typically induced by heat exposure, while HSF1 inhibition and HSF1 knockout reduced these effects. Resveratrol showed the potential to bind to HSF1 and inhibit HSF1 expression in the liver. Moreover, it protected against heat-induced lipid metabolic disorders and necroptosis bothand, in which necroptosis inhibition did not alter lipid metabolism in hepatocytes. Finally, HSF1 inhibitor (KRIBB11) administration protected against heat stroke and liver injury induced by heat exposure, similar to resveratrol. In conclusion, resveratrol protects against heatstroke and complicated liver injury by HSF1-mediated necroptosis, which might be triggered by lipid metabolic disorders. This study provides an intervention strategy for heatstroke and associated complicated liver injury.